Certain drugs are known to produce differential drug effects in the heavily pigmented and lightly pigmented iris. Although melanin pigment may play an important role in the differential drug effects, the types of genetically-dependent pharmacologic receptors in both pigmented and nonpigmented iris are unknown. With the aid of specific receptor binding agents the number and types of cholinergic and adrenergic receptors in both albino and nonalbino rabbit eye will be investigated. Along with the biochemical studies, pharmacologic experiments are also planned. Ototoxicity of many antibiotic aminoglycosides like neomycin, kanamycin, gentamicin and dihydrostreptomycin is at least in part equated with drug binding by the inner ear melanin. Bovine melanin granules, synthetic melanin, and melanoprotein will be used to quantify the binding of the aminoglycosides to the polymers. The relationship between systemic doses and the onset of the retinotoxicity of coulotoxic drugs is unknown. Experiments in both albino and nonalbino animals are planned to quantify the electroretinographic changes produced by the selected drugs.